Weeds cause tremendous global economic losses by reducing crop yields and lowering crop quality. World-wide, agronomic crops must compete with hundreds of weed species.
In spite of the commercial herbicides available today, damage to crops caused by weeds still occurs. Accordingly, there is ongoing research to create more effective and/or more selective herbicidal agents.
Certain benzisoxazole and benzisothiazole herbicidal agents are described in U.S. Pat. Nos. 5,484,763 and 5,523,278. Those patents generically disclose benzisoxazole and benzisothiazole compounds that are substituted in the 3-position with a variety of substituents, none of which are heterocycles. In addition, those patents do not disclose that their compounds are useful for the selective control of weeds in the presence of crops such as corn, soybeans, wheat and transplanted rice.
Surprisingly, it has now been found that benzisoxazole and bensizothazole compounds in which the 3-position is substituted by an optionally substituted heterocycle are more effective and more selective herbicidal agents than expected.
Therefore it is an object of this invention to provide 3-heterocyclic substituted benzisoxazole and benzisothiazole compounds which are highly effective for the control of undesirable plant species.
It is also an object of this invention to provide intermediate compounds useful in the manufacture of said compounds.
It is a further object of the invention to provide a method for the selective control of undesirable plant species in the presence of crops.
These and other objects and features of the invention will become more apparent from the detailed description thereof set forth below.
The present invention provides compounds of formula I 
wherein
Q is selected from 
R is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, cyano, benzyl, OH, NH2, C2-C6 cyanoalkyl and when R and R1 are taken together with the other atoms to which they are attached, they represent a four to seven-membered ring optonally interrupted by oxygen, sulfur or nitrogen and optionally substituted with one to three methyl groups or one or more halogen atoms;
R1 is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, cyano, benzyl, OH, NH2, C2-C6 cyanoalkyl and when R and R1 are taken together with the other atoms to which they are attached, they represent a four to seven-membered ring optionally interrupted by oxygen, sulfur or nitrogen and optionally substituted with one to three methyl groups or one or more halogen atoms;
R2 and R3 are each independently hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, OR8, S(O)mR9 or NR10R11 and when R2 and R3 are taken together with the atoms to which they are attached, they represent a four to seven-membered saturated or unsaturated ring optionally interupted by oxygen, sulfur or nitrogen and optionally substituted with one to three methyl groups or one or more halogen atoms;
R4, R6 and R7 are each independently hydrogen, halogen or C1-C6 alkyl;
R5 is hydrogen, halogen, C1-C6alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C3-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, OR12 or SR13;
R8, R9, R12, R13, and R14 are each independently hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C7 cycloalkyl, C2-C6 cyanoalkyl, benzyl or (subst)phenyl;
R10 is hydrogen, C1-C6alkyl, (subst.)benzyl or (subst.)phenyl, C1-C6 haloalkyl;
R11 is C1-C6alkyl, C1-C6 alkenyl, C3-C6 alkynyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, benzyl, (subst.)phenyl or S(O)nR14;
R88 is cyano, C1-C4 alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkylthio, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl or C1-C4haloalkylsulfonyl;
R89 is hydrogen, cyano, halogen, C1-C4alkyl or C1-C4halolakyl;
n is an integer of 0, 1 or 2;
A, A1 and A2 are each independently oxygen or sulfur;
X is hydrogen, halogen or C1-C4alkyl;
X1 is hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or, C1-C4haloalkoxy;
V is OH, halogen, C1-C4 alkoxy or C1-C4 alkylthio;
Y is an optionally substituted heterocyclic three to seven-membered ring containing one to four heteroatoms selected from oxygen, sulfur or nitrogen;
Z is O or S(O)m;
m is an integer of 0, 1 or 2; and
the optical isomers and diastereomers thereof.
Also provided are intermediate compounds useful in the preparation of the herbicidal formula I compounds.
The present invention further provides herbicidal compositions, and methods.
Surprisingly, it has now been found that the Formula I compounds of the invention demonstrate increased weed control and enhanced crop selectivity. The formula I compounds of the present invention are particularly useful for the selective control of undesirable plant species in the presence of cereal crops such as corn, wheat and rice and in the presence of leguminous crops such as soybeans.
Preferred compounds of the invention are those compounds of formula I wherein
Q is Q7 or Q24;
R is C1-C6 alkyl, C2-C6 alkenyl, C3-C6 alkynyl or NH2;
R2 is C1-C6 alkyl or C1-C6 haloalkyl;
R3 is hydrogen;
Y is selected from 
wherein
R15, R18, R20 and R21 are each independently hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 thioalkyl, halogen, nitro, cyano, hydroxy, C2-C6 alkenyl, C3-C6 alkynyl, C2-C6 haloalkenyl, C3-C8 cycloalkyl or R20 and the carbon on Y to which R20 is attached may form an exocyclic double bond or when R20 and R21 are attached to the same carbon of Y25, R20, R21 and the carbon to which they are bonded may form a three- to six-membered heterocyclic ring;
R16 is hydrogen, halogen, C1-C8 alkyl optionally substituted with C(O)R22, CO2R23, X2R24, S(O)malkyl, NR86R87, C1-C8 haloalkyl, C(O)R25, CO2R26, X3R27, CHxe2x95x90CHR28, C3-C8 cycloalkyl, N(R29)SO2R30, (subst.) phenyl, or when R15 and R16 are attached to adjacent carbon atoms, they may be taken together with the atoms to which they are attched to form a six-membered ring;
R17 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C3-C6 alkynyl, C(O)R25, or(subst.)benzyl;
R19, R29, R33, R34, R35, R37, R38, R39, R42, R43, R44, R46, R47, R48, R50 R51 R52 R53, R55, R56, R57, R60, R61, R62, R64, R65, R66, R69, R70, R71, R73, R74, R75, R76, R80, R85 and R86 are each independently hydrogen, OH, C1-C8 alkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, C2-C8 alkenyl, C3-C6 alkynyl, (subst.) benzyl or (subst.) phenyl;
R23, R26, R31, R40, R49, R58, R67, and R79 are each independently hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C2-C8 alkenyl, C2-C8 haloalkenyl, C5-C8 cycloalkenyl, C5-C8 halocycloalkenyl, C3-C8 alkynyl, C3-C8 haloalkynyl, (subst.)benzyl, (subst.) phenyl, furfuryl, pyridyl, thienyl, an alkali metal, alkaline earth metal, manganese, copper, zinc, cobalt, silver, nickel ammonium or organic ammonium cation;
R22, R25, R32, R36, R41, R45, R54, R59, R63, R68, R72, R77, R78, R81, and R87 are each independently hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C1-C4 cyanoalkyl, benzyl or (subsz.)phenyl;
R24, R27, and R28 are each independently hydrogen,
C1-C10 alkyl optionally substituted with one to six halogens, one C1-C6 alkoxy group, CO2R31, C(O)R32, C(OR33)2, C(SR34)2, C(O)NR35R36, C(O)ONxe2x95x90CR37R38, cyano, (subst.)phenyl or C(O)NHOR39;
C2-C10 alkenyl optionally substituted with one C1-C6 alkyl group, one to three halogens, one C1-C6 alkoxy group, CO2R40, C(O)R41,C(OR42)2, C(SR43)2, C(O)NR44R45, C(O)ONxe2x95x90CR46R47, cyano, (subst.)phenyl or C(O)NHOR48;
C3-C8 cycloalkyl optionally substituted with one C1-C6 alkyl group, one to three halogens, one C1-C6 alkoxy group, CO2R49, C(O) R50, C(OR51)2, C(SR52)2, C(O)NR53R54, C(O)ONxe2x95x90CR55R56, cyano, (subst.)phenyl or C(O) NHOR57;
C5-C8 cycloalkenyl optionally substituted with one C1-C6 alkyl group, one to three halogens, C1-C4 alkoxy group, CO2R58, C(O)R59,C(OR60)2, C(SR61)2, C(O)NR62R63, C(O)ONxe2x95x90CR64R65, cyano, (subst.)phenyl or C(O) NHOR66;
C3-C8 alkynyl optionally substituted with one C1-C6 alkoxy group, CO2R67, C(O)R68,C(OR69)2, C(SR70)2, C(O)NR71R72, C(O)ONxe2x95x90CR73R74, cyano, (subst.)phenyl or CO NHOR75;
phenyl optionally substituted with one to three halogens, one to three C1-C6 alkyl groups, one to three C1-C6 alkoxy groups, one to three C1-C6 haloalkyl groups, one to three C1-C6 haloalkoxy groups, one cyano, one nitro, one NR76R77, one C(O)R78 or one CO2R79;
R30 is OH, C1-C8 alkyl, C3-C8 cycloalkyl, C1-C8 haloalkyl, C2-C8 alkenyl, C2-C8 haloalkenyl, C3-C8 alkynyl, (subst.)benzyl, (subst.) phenyl, or NR80R81;
B and B1 are each independently oxygen, sulfur or NR17;
X2 and X3 are each independently O or S; and the optical isomers and diastereomers thereof.
More preferred, are those compounds of Formula I wherein
Q is Q24;
R is C1-C3 alkyl;
R2 is C1-C3 haloalkyl;
X is hydrogen or halogen;
X1 is hydrogen;
z is sulfur;
Y is selected from Y1, Y2, Y3, Y4, Y5, Y6, Y10, Y11, Y14, Y15, Y16, Y22, Y24, Y25, Y26, Y27, Y28, Y38, and Y39. R15, R18, R20, and R21 are each independently hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, halogen, hydroxy or when R20 and R21 are attached to the same carbon of Y25 an epoxide ring is formed;
R16 is hydrogen, halogen, C1-C3 alkyl optionally substituted with C(O)R22, CO2R23, X2R24, or S(O)malkyl; phenyl; C1-C3 haloalkyl, C(O)R25, CO2R26, X3R27, C3-C8 cycloalkyl, N(R29)SO2R30 or C2-C4 alkenyl;
R17 is hydrogen, C1-C3 alkyl, C2-C4 alkenyl or C(O)R25;
R19, R29 and R80 are each independently hydrogen or C1-C3 alkyl;
R22, R25 and R81 are each independently hydrogen, C1-C3 alkyl, benzyl or (subst)phenyl;
R23, R26 and R31 are each independently hydrogen, C1-C3 alkyl, C2-C4 alkenyl, or C3-C6 alkynyl;
R24 and R27 are each independently hydrogen or C1-C3 alkyl optionally substituted with one CO2R31 group or one C1-C3 alkoxy group;
R30 C1-C3 alkyl, C3-C5 cycloalkyl, C1-C3 haloalkyl, C2-C4 alkenyl (subst.)benzyl, (subst.)phenyl, or NR80R81;
X2 and X3 are O.
Most preferred compounds of the invention are those compounds of formula I wherein
Q is 
Y is selected from 
R15, R18, R20, and R21 are each independently hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy;
R16 is hydrogen, halogen, C1-C8 alkyl optionally substituted with X2R24; C1-C3 haloalkyl, phenyl or C2-C4 alkenyl;
R17 is hydrogen, methyl or C(O)R25;
R19 is hydrogen or C1-C3 alkyl;
R24 is hydrogen or C1-C3 alkyl;
R25 is C1-C3 alkyl or phenyl;
X2 is oxygen.
R88 is preferably C1-C4haloalkyl, C1-C4haloalkoxy or C1-C4alkylsulfonyl, in particular trifluoromethyl or difluoromethoxy, R89 is preferably hydrogen or halogen, in particular chlorine or bromine.
Formula I compounds of the present invention which are particularly effective herbicidal agents include
1-methyl-3-[3-(3-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
ethyl (R)-2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]-4-thiazolidinecarboxylate;
1-methyl-3-[3-(2-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(3-methyl-2-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(1-methylimidazol-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(1-methylpyrrol-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(4-methyl-2-thiazolyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(2,5-diethyl-3-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(2-pyrodyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(3-methoxy-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(3-pyridyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(2-pyrimidinyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-[(1R,2S)-1,2-epoxypropyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(1R,2R)-1,2-epoxypropyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(2-pyridyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil Nxe2x80x3,S,S-trioxide;
1-methyl-3-[3-(5-methyl-1,3,4-oxadiazol-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(5-methyl-1,3,4-thiadiazol-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1,2-benzisothiazole-3-carboxanilide, 4xe2x80x2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-N-methyl-;
1-methyl-3-[3-(3-methyl-2-pyridyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
N-[3-(5-methyl-2-thienyl)-1,2-benzisothiazol-5-yl]-1-cyclohexene-1,2-dicarboximide;
1-methyl-3-[3-(5-methyl-2-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
methyl [(2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]-3-thienyl]oxy]acetate;
methyl 2-[(2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]-3-thienyl]oxy]propionate;
3-[3-(1,3-dithiolan-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[6-fluoro-3-(2-pyridyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(4-methyl-3-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(3,5-dimethyl-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-(3-m-dioxan-2-yl-1,2-benzisothiazol-5-yl)-1-methyl-6-(trifluoromethyl)uracil;
3-acetyl-2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]thiazolidine;
3-benzoyl-2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]thiazolidine;
1-methyl-3-[3-(1,3-oxathiolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(1,3-oxathioln-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil Sxe2x80x2,Sxe2x80x2-dioxide;
1,2-benzisothiazole-3-carboxaldehyde, 5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-, 3-[bis(2-hydroxyethyl) dithioacetal];
1-methyl-3-[3-(1,3-oxathian-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(1,3-oxathian-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil Sxe2x80x2,Sxe2x80x2-dioxide;
3-[3(5,5-dimethyl-m-dioxan-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(4-methyl-m-dioxan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(3-methylpyrazol-1-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethl)uracil;
2-propynyl [[2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]-3-thienyl]oxy]acetate;
3-[3-(4,6-dimethyl-2-pyrimidinyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3-methoxy-2-pyridyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(5-methyl-2-pyridyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(4,6-diethoxy-2-pyrimidinyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[6-fluoro-3-(3-methyl-2-pyridyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
N-[6-fluoro-3-(3-methyl-2-pyridyl)-1,2-benzisothiazol-5-yl]-1-cyclohexene-1,2-dicarboximide;
3-[3-[(4R,5S)-4,5-dimethyl-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,5R)-4,5-dimethyl-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-6-(trifluoromethyl)-3-[3-(3,4,5-trimethyl-pyrazol-1-yl)-1,2-benzisothiazol-5-yl]uracil;
3-[3-[(4R,6S)-4,6-dimethyl-m-dioxan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,6S)-4,6-dimethyl-m-dioxan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3-chloro-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(2-thiazolyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(2-methyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-6-(trifluoromethyl)-3-[3-(4,4,6-trimethyl-m-dioxan-2-yl)-1,2-benzisothiazol-5-yl]uracil;
1-methyl-3-[3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(4-methyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
2,4(1H,3H)-pyrimidinedione, 1-methyl-3-[3-(5-methylene-m-dioxan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)-;
1-methyl-3-[3-(4-methylpyrazol-1-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(2-furyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(1,3-dioxolan-2-yl)-6-fluoro-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-(3-m-dioxan-2-yl-6-fluoro-1,2-benzisothiazol-5-yl)-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,5S)-4,5-dimethyl-1,3-dioxolan-2-yl]-6-fluoro-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil
3-[3-[4-(methoxymethyl)-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3,6-dihydro-4,6,6-trimethyl-2H-pyran-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,5S-)-4,5-dimethyl-1,3-dioxolan-2-yl]-6-fluoro-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,6S)-4,6-dimethyl-m-dioxan-2-yl]-6-fluoro-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
2,4(1H,3H)-pyrimidinedione, 1-methyl-3-[3-(2-methyl-3-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)-;
3-[3-[5-(bromomethyl)-5-hydroxy-m-diaxan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-(3-spiro[m-dioxane-5,2xe2x80x2-oxiran]-2-yl-1,2-benzisothiazol-5-yl)-6-(trifluoromethyl)uracil;
3-[3-(4,4-dimethyl-5-oxo-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[4-(chloromethyl)-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[4-(hydroxymethyl)-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(4-isopropyl-2-oxazolin-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3(2-oxazolin-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-6-(trifluoromethyl)-3-[3-(4-vinyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]uracil;
1-methyl-3-[3-(4-propyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(4-phenyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-[4-(bromethyl)-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[3-(bromomethl)-2-thienyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[3-(methoxymethyl)-2-thienyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3,4-dimethyl-2-thienyl)-1,2-benzisothiazol-5-yl]-i-methyl-6-(trifluoromethyl)uracil;
3-[3-(3-furyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-[4-[(methylthio)methyl]-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-[3-(hydroxymethyl)-2-thienyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-[4-[(methylsulfonyl)methyl]-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-[4-[(methylsulfonyl)methyl]-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-6-(trifluoro-methyl)uracil;
1-methyl-3-[3-[4-[(methylsulfinl)methyl]-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
[2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoro-methyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-l]-1,3-dioxolan-4-yl]methyl thiocyanate;
3-[3-(3,4-dihydro-3-oxo-2-quinoxalinyl)-1,2-benziso-thiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
5-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]-1,6-hydro-6-oxo-2,3-pyrazinedicarbonitrile;
1-methyl-3-[3-(4-oxo-delta-2-1,2,5-thiadiazolin-3-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil Sxe2x80x2,Sxe2x80x2-dioxide;
3-[3-[2-(dimethylamino)-4-methoxy-5-oxo-2-imidazolin-4-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(4-hydroxy-5-oxo-2-phenyl-2-imidazolin-4-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(2-tert-butyl-4-hydroxy-5-oxo-2-imidazolin-4-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(-hydroxy-5-imino-4,4-dimethyl-2-oxo-3-pyrrolidinyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3[4-methoxy-2-(methylimino) 5-oxo-4-imidazolidinyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil; and
3-[3[4-methoxy-2-(ethylimino)-5-oxo-4-imidazolidinyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil.
The Formula I compounds of the present invention are effective herbicidal agents useful for the control of a wide variety of undesirable plant species and for controlling weeds native to both dry land and wet land areas. The inventive compounds are effective in controlling the above-said plants when applied to the foliage thereof or to the soil or water containing seeds or other propagating organs thereof such as stolons, tubers or rhizomes, at rates of from about 0.01 kg/ha to 4 kg/ha and preferably from about 0.01 kg/ha to 1 kg/ha.
Advantageously, it has been found that the compounds of the invention are selective in the presence of soybeans or cereal crops such as corn, wheat and rice when applied preemergence or postemergence.
Beneficially, the formula I compounds may be used for the selective control of undesirable plant species in transplanted rice culture by applying a herbicidally effective amount of a formula I compound to the soil or water containing seeds or other propagating organs of said undesirable plant species after the rice has been transplanted.
Formula I compounds of this invention which are especially useful for the selective control of undesirable plant species in the presence of corn include
1-methyl-3-[3-(3-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(3-chloro-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3,4-dimethyl-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,5S)-4,5-dimethyl-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,5R)-4,5-dimethyl-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil; and
ethyl (R)-2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]-4-thiazolidinecarboxylate.
Formula I compounds of the present invention which are particularly useful for the selective control of undesirable plant species in the presence of wheat include
1-methyl-3-[3-(3-thienyl)-l,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(2-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(3-methyl-2-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil
1-methyl-3-[3-(5-methyl-2-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(3-chloro-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3,4-dimethyl-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(2,5-diethyl-3-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3-methoxy-2-pyridyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,5S)-4,5-dimethyl-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,5S)-4,5-dimethyl-1,3-dioxolan-2-yl]-6-fluoro-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[4-(hydroxymethyl)-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-6-(trifluoromethyl)-3-[3-(4-vinyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]uracil;
1-methyl-3-[3-(4-propyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-[4-(bromethyl)-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(4-isopropyl-2-oxazolin-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil; and
ethyl (R)-2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]-4-thiazolidinecarboxylate.
Formula I compounds of this invention which are particularly useful for the selective control of undesirable plant species in the presence of soybeans include
1-methyl-3-[3-(3-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(3-Methoxy-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(5-methyl-2-thienyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(3-chloro-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3,4-dimethyl-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3-methoxy-2-pyridyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(5-methyl-2-pyridyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-[4-(hydroxymethyl)-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(2-pyrimidinyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-[(4R,6S)-4,6-dimethyl-m-dioxan-2-yl]-6-fluoro-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil; and
3-[3-(4-isopropyl-2-oxazolin-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil.
Formula I compounds of this invention which are particularly useful for the selective control of undesirable plant species in the presence of transplanted rice include
1-methyl-3-[3-(5-methyl-2-thienyl)-l,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(3-chloro-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[3-(methoxymethyl)-2-thienyl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3,4-dimethyl-2-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(2,5-diethyl-3-thienyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[6-fluoro-3-(2-pyridyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(3-methoxy-2-pyridyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(5-methyl-2-pyridyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[6-fluoro-3-(3-methyl-2-pyridyl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-(1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,5S)-4,5-dimethyl-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(2-methyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-[(4R,5S)-4,5-dimethyl-1,3-dioxolan-2-yl]-6-fluoro-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-6-(trifluoromethyl)-3-[3-(4-vinyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]uracil;
1-methyl-3-[3-(4-propyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(4-isopropyl-2-oxazolin-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(2-thiazolyl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil; and
ethyl (R)-2-[5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl]-4-thiazolidinecarboxylate.
Formula I compounds of this invention which are particularly useful for total vegetation control include
3-[3-(1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
1-methyl-3-[3-(4-methyl-1,3-dioxolan-2-yl)-1,2-benzisothiazol-5-yl]-6-(trifluoromethyl)uracil;
3-[3-(1,3-dioxolan-2-yl)-6-fluoro-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[4-(methoxymethyl)-1,3-dioxolan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,5S-)-4,5-dimethyl-1,3-dioxolan-2-yl]-6-fluoro-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil;
3-(3-m-dioxan-2-yl-1,2-benzisothiazol-5-yl)-1-methyl-6-(trifluoromethyl)uracil;
3-[3-[(4R,6S)-4,6-dimethyl-m-dioxan-2-yl]-1,2-benzisothiazol-5-yl]-1-methyl-6-(trifluoromethyl)uracil; and
3-(3-m-dioxan-2-yl-6-fluoro-1,2-benzisothiazol-5-yl)-1-methyl-6-(trifluoromethyl)uracil.
While the compounds of this invention are effective for controlling undesirable plant species when employed alone, they may also be used in combination with or in conjunction with one or more other biological chemicals, including herbicides.
The compounds of this invention may be applied to the foliage of undesirable plant species or to the soil or water containing seeds or other propagating organs thereof in the form of a solid or liquid herbicidal composition, comprising a herbicidally effective amount of the desired compound dispersed or dissolved in an agronomically acceptable, inert solid or liquid carrier. The compositions may be applied as preemergence or postemergence treatments.
The formula I compounds of the present invention may be formulated as emulsifiable concentrates, wettable powders, granular formulations, suspension concentrates, flowable concentrates and the like.
Formula I compounds wherein Q is Q1, Q2, Q3, Q5, Q6, Q7, Q9, Q10, Q11, Q12, Q13, Q14, Q16, Q17, Q18, Q19, Q20, Q22, Q24, Q25, Q36 and Q40 may be prepared from 5-aminobenzisothiazoles and 5-aminobenzisoxazoles of Formula II 
wherein X, X1, Z and Y are as described hereinabove, using essentially the same procedures as described in U.S. Pat. Nos. 5,484,763 and 5,523,278.
Formula I compounds wherein Q is Q8 may be prepared by reacting an amine of formula II with a substituted tetrahydrofuran of formula III as shown below in Flow Diagram I. 
Formula I compounds wherein Q is Q4 may be prepared from formula I compounds wherein Q is Q8 using essentially the same procedures used to prepare formula I compounds wherein Q is Q3 from formula I compounds wherein Q is Q7.
Compounds of formula I wherein Q is Q15 may be prepared by reacting an amine of formula II with a substituted tetrahydrofuran of formula III to form an acid-amide of formula IV, and dehydrating the acid-amide with a dehydrating agent such as 1,3-dicyclohexyl-carbodiimide. The reaction scheme is shown below in Flow Diagram II. 
Formula I compounds wherein Q is Q21 may be prepared from formula I compounds wherein Q is Q8 using essentially the same procedure used to prepare formula I compounds wherein Q is Q20 from formula I compounds wherein Q is Q7.
Compounds of formula I wherein Q is Q23 may be prepared by converting an amine of formula II to its corresponding isocyanate or isothiocyanate of formula V using standard methods such as phosgene or thiophosgene in an inert solvent or palladium chloride and carbon monoxide, reacting the formula V compound with a substituted hydrazine of formula VI to form an intermediate compound of formula VII, and reacting the formula VII compound with an ester of formula VIII. The reaction scheme is shown in Flow Diagram III. 
Formula I compounds wherein Q is Q26 may be prepared by reacting an amine of formula II with a xcex2-aminoacrylic acid chloride of formula IX to form an intermediate compound of formula X, and reacting the intermediate compound with an acid chloride of formula XI. The reaction scheme is shown in Flow Diagram IV. 
Compounds of formula I wherein Q is Q27 may be prepared by reacting an amine of formula II with an acid chloride of Formula XII to form an intermediate compound of formula XIII, and reacting the intermediate compound (after deprotection) with an acid chloride of formula XI. The reaction sequence is shown below in Flow Diagram V. 
Formula I compounds wherein Q is Q28 may be prepared by reacting an amine of formula II with an unsaturated lactone of formula XIV as shown below in Flow Diagram VI. 
Similarly, formula I compounds wherein Q is Q29 may be prepared by reacting an amine of formula II with a lactone of formula XV. The reaction scheme is shown in Flow Diagram VII. 
Compounds of formula I wherein Q is Q30 may be prepared, as shown in Flow Diagram VIII, by reacting an isocyanate or isothiocyanate of formula V with an unsaturated lactone of formula XVI at an elevated temperature. 
Similarly, formula I compounds wherein Q is Q31 may be prepared by reacting an isocyanate or isothiocyanate of formula V with a lactone of formula XVII at an elevated temperature. The reaction scheme is shown in Flow Diagram IX. 
Formula I compounds wherein Q is Q34 may be prepared, as shown in Flow Diagram X, by reacting an isocyanate or isothiocyanate of formula V with a substituted hydrazine of formula XVIII to form an intermediate compound of formula XIX, and reacting the formula XIX compound with an acetal of formula XX at an elevated temperature. 
Formula I compounds wherein Q is Q37 may be prepared, as shown in Flow Diagram XI, by reacting an isocyanate or isothiocyanate of formula V with an amine of formula XXI to form an intermediate of formula XXII, and reacting the intermediate with an xcex1-haloketone of formula XXIII. 
Compounds of formula II wherein Q is Q38 may be prepared, as shown below in Flow Diagram XII, by reacting a urea or thiourea of formula VII with an acid chloride of formula XXIV. 
Formula I compounds wherein Q is Q39 may be prepared by reacting an amine of formula II with a chloride compound of formula XXV to form an intermediate compound of formula XXVI, and reacting the intermediate compound with hydrogen sulfide, hydrogen chloride and sodium periodate. The reaction scheme is shown in Flow Diagram XIII. 
Compounds of formula I wherein Q is Q35 may be prepared from amine compound II by treatment with nitrous acid to form an intermediate diazonium salt XXVII followed by treatment with cuprous cyanide and heating to afford intermediate cyano compound of formula XXVIII. Treatment of intermediate cyano compound XXVIII with a substituted hydrazine of formula VI to form an intermediate compound of formula XXIX, and reacting the intermediate compound with an acid chloride of formula XXX. The reaction scheme is show in Flow Diagram XIV. 
Compounds of formula I wherein Q is Q33 may be prepared, as shown in Flow Diagram XV, by acylating a compound of formula XXXI with acetyl chloride and aluminum chloride to form an acetophenone of formula XXXII, reacting the acetophenone compound with an ester of formula XXXIII in the presence of a base to form a diketone compound of formula XXXIV, and reacting the formula XXXIV compound with a substituted hydrazine of formula VI. 
Further methods to prepare compound I with Q=Q33 may be taken from EP-A361,164 and WO92/02503 Compounds of formula I wherein Q is Q32 may be prepared as shown in Flow Diagram XVI by reacting an isocyanate or isothiocyanate of formula V with an amidine of formula XXXV to form an intermediate of formula XXXVI, reacting the formula XXXVI compound with phosgene or thiophosgene to form an intermediate of formula XXXVII, and alkylating the formula XXXVII compound with a halide of formula XXXVIII. 
A preferred method for the preparation of formula I compounds wherein Q is Q24 is shown in Flow Diagram XVII, wherein an amine of formula II is reacted with an oxazinone of formula XXXIX in the presence of an organic acid or base to form an intermediate compound of formula XL, which is alkylated with a halide of formula XXXVIII. 
Formula I compounds wherein Q is Q24 and the intermediates of formula XL may also be prepared from the amines II by using essentially the same procedures as described in W) 97/08171, WO 99/14216, WO 00/28822 amd DE-A 197,195.
Another preferred method for the preparation intermediates of formula XL is shown in Flow Diagram XVIII, by reaction of an amine of formula II with a urea of Formula XLI in the presence of an acid or base, wherein R82 and R83 are each independently C1-C6 alkyl or R82 and R83 may be taken together with the atom to which they are attached to form a 5-or 6-membered ring optionally containing one oxygen atom. 
The compound of Formula XL is then reacted in the presence of Base with a compound of Formula XXXVIII (RX3, where X3 is Cl, Br, I) to obtain the compound of Formula I wherein Q is Q24.
An alternate method for the preparation of formula I compounds wherein Q is Q24 is shown in Flow Diagram XIX, wherein an amine of formula II is reacted with a carbamate of formula XLII wherein R84 is C1-C6 alkyl, benzyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C7 cycloalkyl and Z2 is C1-C6 alkyl. 
5-Aminobenzisothiazole and 5-aminobenzisoxazole compounds of formula II can be prepared by reduction of 5-nitro intermediates of formula XLIV as shown in Flow Diagram XX using standard conditions such as iron in acetic acid, stannous chloride and hydrochloric acid, or dithionite. The 5-nitro intermediates XLIV can be prepared from ketones of formula XLIII by methods described in U.S. Pat. No. 5,484,763, also shown in Flow Diagram XX. 
Alternatively, 5-aminobenzisothiazoles of formula II may be prepared as shown in Flow Diagram XXI. Nitration of ketones of formula XLV followed by reduction of the resulting intermediates XLVI affords amines of formula XLVII. Treatment of formula XLVII compounds with sodium isothiocyanate and bromine in the presence of acid affords intermediate isothiocyanate compounds of formula XLVIII, which on treatment with ammonium hydroxide in methanol afford 5-aminobenzisothiazole compounds of formula II (Z=S). 
Ketones of formula XLIII where Y is Y1 may be prepared by reaction of organolithium reagents XLIX with zinc chloride followed by coupling with acid chloride LI in the presence of a palladium catalyst as shown in Flow Diagram XXII. Under essentially the same conditions, ketones of formula XLIII where Y is Y2 are prepared from organometallic reagents L. Organometallic reagents XLIX and L may be prepared by standard methods such as direct deprotonation of the heterocycle Y, or by halogen-metal exchange with a halogenated heterocycle Y. 
Ketones of formula XLIII wherein Y1 is a substituted 2-furanyl radical may additionaly be prepared by reaction of organotin reagent LII with acid chloride LI as shown in Flow Diagram XXIII. 
Ketones of formula XLIII wherein Y1 is a substituted 2- or 3-thienyl radical may additionally be prepared by reaction of thiophene LIV with acid chloride LI, in the presence of a Lewis acid such as aluminum chloride as shown in Flow Diagram XLIII. Alternatively, ketones of formula XLIV wherein Y1 is a substituted 2-thienyl radical may be prepared by treatment of acid LIII with thiophene LIV in the presence of phosphorous pentoxide. 
Ketones of formula XLIII wherein Y is Y3 may be prepared by treatment of nitrile LV with lithiated pyridine LVI followed by acid hydrolysis to afford intermediate ketone compound LVII, which is nitrated under standard conditions as depicted in Flow Diagram XXV. Lithiated pyridine XLVI may be prepared from the corresponding bromopyridine by treatment with n-butyllithium. 
Ketones of formula XLIII wherein Y is Y5 may be prepared by heating nitrile LVIII with bromopyrimidine LIX to afford intermediate LX, which on oxidation yields ketone LXI, which can be nitrated as depicted in Flow Diagram XXVI. 
The aformentioned nitro ketones of formula XLIII where where Y is Y1, Y2, Y3 and Y5 may be converted into nitro intermediate XLIV and amino intermediate II by the methods shown in Flow Diagram XX.
Ketones of formula XLV wherein Y is Y3 may be prepared by reaction of nitrile LXII with organolithium reagent LXIV followed by hydrolysis under acidic conditions as shown in Flow Diagram XXVII. Alternatively, ketones XLV wherein Y is Y3 may be prepared by reaction of Grignard reagent LXIII with pyridylnitrile LXV followed by hydrolysis under acidic conditions as shown in Flow Diagram XXVII. 
The aforementioned ketones XLV wherein Y is Y3 may be converted to 5-aminobenzisoxazoles and 5-aminobenzthiazoles wherein Y is Y3 by the method outlined in Flow Diagram XXI.
Compounds of formula I wherein Y is Y2 and B=S additionally may be prepared by treatment of thioamide LXVI with a bromoketone of formula LXVII in the presence of base as shown in Flow Diagram XXVIII. 
Intermediate thioamide compound of formula LXVI can be prepared by standard methods such as treatment amide compound of formula LXX with Lawesson""s reagent or phosphorous pentasulfide. Formula LXX amides are prepared from acid LXVIII by treatment of its acid chloride derivative LXIX with ammonia as depicted in Flow Diagram XXIX. 
Intermediate acid compounds of formula LXVIII may be prepared by bromination of methyl intermediate LXXI to afford a mixture of monobromo (LXXII) and dibromo (LXXIII) intermediate compounds, subsequent oxidation of this mixture with silver tetrafluoroborate to afford a mixture of alcohol LXXIV and aldehyde LXXV, and final oxidation of this mixture with potassium dichromate in the presence of acid as shown in Flow Diagram XXX. 
Compounds of formula I where Y=Y5 may additionally be prepared by oxidation of intermediate dibromo compound LXXIII to aldehyde LXXV followed by reaction with diketone LXXVI or imino ester LXXVII as depicted in Flow Diagram XXXI. 
Compounds of formula I wherein Y is Y4 may be prepared by oxidation of pyridyl compounds of formula I (Y=Y3) with peracid under standard conditions as shown in Flow Diagram XXXII. 
Nitro intermediates XLIV and benzisothiazoles and benzisozaxoles II wherein Y is Y6 may be prepared from 3-chloro intermediate compounds LXXVIII and LXXIX respectively by treatment with pyrazole LXXX in the presence of an organic base as shown in Flow Diagram XXXIII. 
Nitro intermediate compounds LXXVIII are prepared from acid intermediate LIII by conversion to disulfide LXXXI by sequential treatment with base, sodium sulfide, and acid as depicted in Flow Diagram XXXIV. Intermediate disulfide compound LXXXI is converted to intermediate benxisothiazolone LXXXII by sequential treatment with thionyl chloride, bromine and ammonia, and this product then treated with phosphorous oxychloride in the presence of base. 
Benzisothiazole and benzisozaxole intermediate compound LXxix is prepared as shown in Flow Diagram XXXV from nitro intermediate LXXVIII by reduction to amino intermediate LXXXIII under standard conditions such as iron in the presence of acid, followed by elaboration of the amino functionality to Q groups as described in U.S. Pat. Nos. 5,484,763, 5,523,278 and Flow Diagrams I-XIX. 
Compounds of formula I wherein Y is Y7 and Y8 may be prepared as shown in Flow Diagram XXXVI by treatment of acid chloride intermediate compound LXIX with organozinc reagent of formula LXXXIV to afford intermediate ketone compound LXXXV, which is acylated with acid chloride LXXXVI in the presence of base to afford intermediate diketone of formula LXXXVII. Diketone LXXXVII is treated with hydrazine to afford a mixture of pyrazole regioisomers LXXXVIII and LXXXIX, which is alkylated with an alkyl halide of formula XC to yield a mixture of regioisomeric pyrazoles which can be separated by column chromatography or fractional crystallization. 
Compounds of formula I wherein Y is Y9 may be prepared as shown in Flow Diagram XXXVII by bromination of intermediate ketone of formula LXXXV and subsequent treatment of bromoketone intermediate XCI with thioamide XCII. 
Compounds of formula I wherein Y is Y10 may be prepared as shown in Flow Diagram XXXVIII by reaction of acid chloride intermediate LXIX with amine compound XCIII to afford intermediate amide XCIV, which on sequential treatment with thionyl chloride followed by sodium hydride yields the compound of formula I wherein B=O. Alternatively, treatment of amide XCIV with phosphorous pentasulfide yields thioamide compound XCV, which on treatment with sodium hydride yields the compound wherein B=S. Treatment of amide XCIV with amine XCVI under dehydrating conditions affords compound I wherein B=NR17. 
Compounds of formula I wherein Y is Y11 may be prepared as shown in Flow Diagram XXXIX by reaction of acid chloride LXIX with hydrazide XCVII to afford Intermediate hydrazide of formula XCVIII, which on treatment with phosphorous oxychloride and phosphorous pentasulfide yields compounds of formula I wherein B=O and B=S respectively. 
Treatment of acid chloride LXIX with amide XCIX affords amide intermediate C, which on treatment with hydrazine in the presence of acid yields triazole intermediate CI. Alkylation of triazole intermediate CI with alkyl halide XC affords compounds of formula I wherein Y=Y11 and B=NR17 as shown in Flow Diagram XL. 
Alternatively nitro intermediates XLIV wherein Y=Y11 and B=O and B=S can be prepared as depicted in Flow Diagram XLI by conversion of acid chloride CII to hydrazide intermediate CIII with hydrazide reagent XCVII and subsequent treatment with phosphorous oxychloride and phosphorous pentasulfide, respectively. 
Acid chloride CIV may be prepared as outlined in Flow Diagram XLII. Treatment of thiophenol CIV with oxalyl chloride followed by aluminum chloride affords thiodione CV, which on treatment with ammonium hydroxide and hydrogen peroxide yields amide CVI. Basic hydrolysis of amide CVI affords acid CVII, which is nitrated under standard conditions to afford acid CVIII. Treatment of acid CVIII with thionyl chloride affords acid chloride CII. 
Compounds of formula I wherein Y is Y12 may be prepared as shown in Flow Diagram XLIII by treatment of intermediate LXXIX with hydrazine to produce hydrazino intermediate CIX and subsequent treatment of this with amide CX. 
Compounds of formula I wherein Y is Y13 may be prepared as shown in Flow Diagram XLIV by conversion of aldehyde LXXV to chloro intermediate CXI, and subsequent treatment of this intermediate with an olefin CXII in the presence of a base such as triethylamine. 
Compounds of formula I wherein Y is Y14 may be prepared by treatment of ketoester CXIII with sulfamide to afford intermediate of structural formula CXIV, and subsequent alkylation with alkyl halide XL as shown in Flow Diagram XLV. 
Intermediate ketoester CXIII is prepared from chloro intermediate LXXVIII by treatment with cyanoacetic ester in the presence of base to afford intermediate cyanoester CXV which on treatment with acetyl chloride affords nitro ester CXVI. Reduction of nitro ester CXVI with iron in acetic acid affords amino ester CXVII which can be elaborated into an intermediate ester of formula CXVIII by the methods described in Flow Diagrams I-XIX. Oxidation of ester CXVIII with selenium dioxide affords ketoester CXIII as shown in Flow Diagram XLV wherein R85 is C1-C6 alkyl, benzyl, C2-C6 alkenyl, C2-C6 alkynyl, or C3-C7 cycloalkyl. 
Compounds of formula I wherein Y is Y15 or Y16 may be prepared as outlined in Flow Diagram XLVII by treatment of keto ester CXIII with amidine CXIX and amidine or quanidine CXX, respectively 
Compounds of formula XLIV wherein Y is Y17 or Y18 may be prepared as shown in Flow Diagram XLVIII. Acylation of ketone CXXI with ester CXXII in the presence of base affords intermediate keto ester CXXIII, which on treatment with hydrazine yields intermediate CXXIV, which can be alkylated with alkyl halide XL to afford compound XLIV wherein Y is Y17. Oxidation of intermediate CXXIV with bromine yields intermediate CXXV which can be alkylated with alkyl halide XL to afford compound XLIV wherein Y is Y18. Ketone CXXI can be prepared from acid chloride CII using the method described in Flow Diagram XXXVI for the synthesis of ketone LXXXV. 
Compounds XLIV wherein Y is Y19 can be prepared as depicted in Flow Diagram XLIX by alkylation of ketone CXXI with alkyl halide CXXVI in the presence of base and subsequent hydrolysis to afford intermediate keto aldehyde CXXVII, which is treated with hydrazine and oxidized as shown. 
Compounds XLIV wherein Y is Y20 may be prepared by treatment of the anion of ester CXVI with paraformalde-hyde followed by oxidation of the hydroxy ester product to ester aldehyde CXXVIII as shown in Flow Diagram L. Treatment of ester aldehyde intermediate CXXVIII with amidine CXX with a reducing agent such as di-isobutyl aluminum hydride (DIBAL) in an inert solvent in the presence of base affords intermediate CXXIX, which can be alkylated with alkyl halide XL as shown. 
Compounds wherein Y is Y21 may be prepared as shown in Flow Diagram LI by treatment of chloro intermediate LXXVIII with malononitrile in the presence of base to afford intermediate dinitrile CXXX. Reduction of dinitrile CXXX with a reducing agent such as di-isobutyl aluminum hydride (DIBAL) affords dialdehyde CXXXI, which is treated with amidine CXX as shown. 
Compounds I wherein Y is Y22 and Y23 are prepared by treatment of keto ester CXIII with olefin CXXXII to afford intermediate CXXXIII, which is treated with phosphorous oxychloride or alkylated with alkyl halide LX as depicted in Flow diagram LII. 
The syntheses of compounds I wherein Y is Y24 through Y27 are depicted in Flow Diagram LIII. Coupling of acid chloride LXIX with organozinc reagent CXXXIV in the presence of a palladium catalyst affords ketone CXXXV, which on treatment with CXXXVI under dehydration conditions yields compounds I wherein Y is Y24. Compounds I wherein Y is Y24, B is O, and B1 is sulfur can be oxidixed to compound I wherein Y is Y25. In similar fashion, intermediate ketone CXXXV can be reacted with intermediate CXXXVII to afford compound I wherein Y is Y26, and this compound wherein B is O, and B1 is S can be oxidized to compound I wherein Y is Y27. 
Alternatively, compounds I wherein Y is Y24 and both B and B1 are oxygen can be prepared by treatment of dibromo intermediate LXXIII with dial CXXXVI in the presence of a silver salt such as silver trifluoromethanesulfonate as shown in Flow Diagram LIV. 
Compounds wherein Y is Y28 can be prepared by treatment of aldehyde LXXV with diol CXXXVIII in the presence of acid with azeotropic removal of water as shown in Flow Diagram LV. 
Compounds I wherein Y is Y29 and Y30 can be prepared by treatment of ketone CXXXV with hydroxy acids CXXXIX and CXL, respectively, under acidic conditions with azeotropic removal of water as shown in Flow Diagram LVI. 
Compounds wherein Y is Y31 and Y33 can be prepared from keto ester CXLI by conversion to diol CXLIII by reduction for the case wherein R15(16) is hydrogen, or by reaction with organolithium reagent CXLII followed by reduction for the case wherein R15(16) is not hydrogen, and subsequent reaction of diol intermediate CXLIII with aldehyde CXLIV in the presence of acid, with azeotropic removal of water or by reaction with phosgene or thiophosgene as shown in Flow Diagram LVII. 
Keto ester CXXXII can be prepared from chloro intermediate LXXVIII using the procedure described in Flow Diagram XLV.
Compound XLIV wherein Y is Y32 and Y34 can be prepared from chloro intermediate LXXVIII by treatment with a dialkyl malonate in the presence of base to form diester CXLV, which can be alkylated with alkylating agent CXLVI to produce diester CXLVII. Diester CXLVII can be reduced to diol CXLVIII, which is treaed with aldehyde CXLIV in the presence of acid with azeotropic removal of water, or with phosgene or thiophosgene as depicted in Flow Diagram LVIII. 
Compounds I wherein Y is Y35 may be prepared reaction of the anion of ester CXVIII with aldehyde CXLIV to generate diol intermediate CXLIX, which is treated with aldehyde CL in the presence of acid with azeotropic removal of water as depicted in Flow Diagram LIX. 
Compounds I wherein Y is Y36 may be prepared reaction of the anion of methyl ketone CXXXV (R19=CH3) with aldehyde CXLIV, followed by reduction with agents such as sodium borohydride for the case wherein R15(16) is hydrogen, or reaction with organolithium reagent CXLII for the case wherein R15(16) is not hydrogen, which affords diol intemediate CLI which is reacted with phosgene in the presence of a base as depicted in Flow Diagram LX. 
Compounds I wherein Y is Y37 may be prepared by conversion of ester CXVIII to acid chloride CLII by sequential treatment with aqueous sodium hydroxide, N-chlorosuccinimide or N-bromosuccinimide, and oxalyl chloride. Treatment of acid chloride CLII with reagent CLIII in the presence of base affords compound I wherein Y is Y37. 
Compounds I wherein Y is Y38 may be prepared by conversion of diol CXLIII to halo intermediate CLIV and subsequent treatment with reagent CLV in the presence of a silver salt as depicted in Flow Diagram LXII. 
Compounds I wherein Y is Y39 and Y40 may be prepared by epoxidation of olefin CLVI and conversion of epoxide I (Y=Y39) to aziridine as depicted in Flow Diagram LXIII. 
The present invention also relates to intermediate compounds of formula XL, formula XLIV or formula II 
wherein R2, R3X X1, Y and Z are as defined above for formula I.
Preferred intermediate compounds of formula XL, XLIV and II are those compounds wherein Y is 
wherein
R15, R18, R20 and R21 are each independently hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 thioalkyl, halogen, nitro, cyano, hydroxy, C2-C6 alkenyl, C3-C6 alkynyl, C2-C6 haloalkenyl, C3-C8 cycloalkyl or R20 and the carbon on Y to which R20 is attached may form an exocyclic double bond or when R20 and R21 are attached to the same carbon of Y25, R20, R21 and the carbon to which they are bonded may form a three- to six-membered heterocyclic ring;
R16 is hydrogen, halogen, C1-C8 alkyl optionally substituted with C(O)R22, CO2R23, X2R24, S(O)malkyl, NR86R87, C1-C8 haloalkyl, C(O)R25, CO2R26, X3R27, CHxe2x95x90CHR28, C3-C8 cycloalkyl, N(R29)SO2R30 or (subst.) phenyl;
When R15 and R16 are attached to separate adjacent carbons, as in Y24, they may form a six-membered heterocyclic or carbocyclic ring fused to the Y-ring;
R17 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C3-C6 alkynyl, C(O)R25, or(subst.)benzyl;
R19, R29, R33, R34, R35, R37, R38, R39, R42, R43, R44, R46, R47, R48,
R50, R51, R52, R53, R55, R57, R60, R61, R62, R64, R65, R66, R69, R70, R71, R73, R74, R75, R76, R80, and R85 are each independently hydrogen, OH, C1-C8 alkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, C2-C8 alkenyl, C3-C6 alkynyl, (subst.) benzyl or (subst.) phenyl;
R22, R25, R32, R36, R41, R45, R54, R59, R63, R68, R72R77, R78, R81, and R87 are each independently hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C1-C4 cyanoalkyl, benzyl or (subst.)phenyl;
R23, R26, R31, R40, R49, R58, R67, and R79 are each independently hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C2-C8 alkenyl, C2-C8 haloalkenyl, C5-C8 cycloalkenyl, C5-C8 halocycloalkenyl, C3-C8 alkynyl, C3-C8 haloalkynyl, (subst.)benzyl, (subst.) phenyl, furfuryl, pyridyl, thienyl, an alkali metal, alkaline earth metal, manganese, copper, zinc, cobalt, silver, nickel ammonium or organic ammonium cation;
R24, R27, and R28 are each independently hydrogen,
C1-C10 alkyl optionally substituted with one to six halogens, one C1-C6 alkoxy group, CO2R31, C(O)R32, C(OR33)2, C(SR34)2, C(O)NR35R36, C(O)ONxe2x95x90CR37R38, cyano, (subst.)phenyl or C(O)NHOR39;
C2-C10 alkenyl optionally substituted with one C1-C6 alkyl group, one to three halogens, one C1-C6 alkoxy group, CO2R40, C(O)R41, C(OR42)2, C(SR43)2, C(O)NR44R45, C(O)ONxe2x95x90CR46R47, cyano, (subst.)phenyl or C(O)NHOR48;
C3-C8 cycloalkyl optionally substituted with one C1-C6 alkyl group, one to three halogens, one C1-C6 alkoxy group, CO2R49, C(O)R50, C(OR51)2, C (SR52)2, C(O)NR53R54, C(O)ONxe2x95x90CR55R56, cyano, (subst.)phenyl or C(O)NHOR57;
C5-C8 cycloalkenyl optionally substituted with one C1-C6 alkyl group, one to three halogens, C1-C4 alkoxy group, CO2R58, C(O)R59, C(OR60)2, C(SR61)2, C(O)NR62R63, C(O)ONxe2x95x90CR64R65, cyano, (subst.)phenyl or C(O)NHOR66;
C3-C8 alkynyl optionally substituted with one C1-C6 alkoxy group, CO2R67, C(O)R68,C(OR69)2, C(SR70)2, C(O)NR71R72, C(O)ONxe2x95x90CR73R74, cyano, (subst.)phenyl or C(O)NHOR75;
phenyl optionally substituted with one to three halogens, one to three C1-C6 alkyl groups, one to three C1-C6 alkoxy groups, one to three C1-C6 haloalkyl groups, one to three C1-C6 haloalkoxy groups, one cyano, one nitro, one NR76R77, one C(O)R78 or one CO2R79;
R30 is OH, C1-C8 alkyl, C3-C8 cycloalkyl, C1-C8 haloalkyl, C2-C8 alkenyl, C2-C8 haloalkenyl, C3-C8 alkynyl, (subst.)benzyl, (subst.) phenyl, or NR80R81;
B and B1 are each independently oxygen, sulfur or NR17; and
X2 and X3 are each independently O or S; or the optical isomers or diastereomers thereof.
More preferred formula XL, XLIV and II intermediate compounds of this invention are those compounds wherein
R2 is C1-C3 haloalkyl;
X is hydrogen or halogen;
X1 is hydrogen;
Z is sulfur;
Y is Y1, Y2, Y3, Y4, Y5, Y6, Y10, Y11, Y14, Y15, Y16, Y22, Y24,
Y25, Y26, Y27, Y28, Y38, or Y39;
R15, R18, R20, and R21 are each independently hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, halogen, hydroxy or when R20 and R21 are attached to the same carbon of Y25 an epoxide ring is formed;
R16 is hydrogen, halogen, C1-C3 alkyl optionally substituted with C(O)R22, CO2R23, X2R24, or S(O)malkyl; phenyl; C1-C3 haloalkyl, C(O)R25, CO2R26, X3R27, C3-C8 cycloalkyl, N(R29)SO2R30 or C2-C4 alkenyl;
R17 is hydrogen, C1-C3 alkyl, C2-C4 alkenyl or C(O)R25;
R19, R29 and R80 are each independently hydrogen or C1-C3 alkyl;
R22, R25 and R81 are each independently hydrogen, C1-C3 alkyl, benzyl or (subst)phenyl;
R23, R26 and R31 are each independently hydrogen, C1-C3 alkyl, C2-C4 alkenyl, or C3 -C6 alkynyl;
R24 and R27 are each independently hydrogen or C1-C3 alkyl optionally substituted with one CO2R31 group or one C1-C3 alkoxy group;
R30 C1-C3 alkyl, C3-C5 cycloalkyl, C1-C3 haloalkyl, C2-C4 alkenyl (subst.)benzyl, (subst.)phenyl, or NR80R81;
X2 and X3 are O.
Most preferred compounds of formula XL, XLIV and II are those compounds wherein
R2 is trifluoromethyl;
Z is S;
Y is 
R15, R18, R20, and R21 are each independently hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy;
R16 is hydrogen, halogen, C1-C8 alkyl optionally substituted with X2R24; C1-C3 haloalkyl, phenyl or C2-C4 alkenyl;
R17 is hydrogen, methyl or C(O)R25;
R19 is hydrogen or C1-C3 alkyl;
R24 is hydrogen or C1-C3 alkyl;
R25 is C1-C3 alkyl or phenyl; and
X2 is oxygen.
The present invention also provides intermediate compounds of formula CXIII 
wherein Q, X, X1, and Z are defined as above for formula I and R85 is C1-C6 alkyl, benzyl, C2-C6 alkenyl, C2-C6 alkynyl, or C3-C7 cycloalkyl.
Preferred compounds of formula CXIII are those wherein
Q is Q7 or Q24;
R is C1-C6 alkyl, C2-C6 alkenyl, C3-C6 alkynyl or NH2;
R2 is C1-C6 alkyl or C1-C6 haloalkyl;
R3 is hydrogen; and
R85 is C1-C6 alkyl.
More preferred compounds of formula CXIII are those wherein
Q is Q24;
R is C1-C3 alkyl;
R2 is C1-C3 haloalkyl;
Z is sulfur;
X is hydrogen or halogen; and
X1 is hydrogen.
Most preferred compounds of formula CXIII are those wherein
Q is 
and
Z is sulfur.
In order to facilitate a further understanding of the invention, the following examples are presented to illustrate more specific details thereof. The invention is not to be limited thereby except as defined in the claims. The terms NMR and IR designate nuclear magnetic resonance and infrared, respectively.